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J Thorac Cardiovasc Surg 1995;110:22-26
© 1995 Mosby, Inc.
CARDIAC AND PULMONARY REPLACEMENT |
Toronto, Ontario, Canada
Received for publication Oct. 28, 1994. Accepted for publication Dec. 20, 1994. Address for reprints: J. R. Maurer, MD, FRCP(C), EN10-220, Toronto General Hospital, 200 Elizabeth Street, Toronto, Ontario M5G 2C4, Canada.
Abstract
Pleural complications occurred in 30 (22%) of 138 patients after 53 single and 91 double lung transplants between September 1986 and February 1993. These were defined for the purposes of this study as pneumothorax persisting beyond the first 14 postoperative days, recurrent pneumothorax, or any other pleural process that necessitated diagnostic or therapeutic intervention. Overall, a higher pleural complication rate was seen in double lung transplantation (25 of 30) than in single lung transplantation (5 of 30) with no differences noted in the frequency among preoperative diagnostic groups (p > 0.05). Pneumothorax was the most frequent complication, affecting 14 of 30 patients, with 6 of 14 cases occurring after transbronchial biopsy. All pneumothoraces in single (n = 4) and double lung transplantation (n = 10) resolved spontaneously or with chest tube thoracostomy. One patient required placement of a Clagett window after open lung biopsy and another required thoracotomy and pleural abrasion after transbronchial biopsy. Parapneumonic effusion was observed in 4 of 30 double lung transplantations with spontaneous resolution in all cases. Empyema affected 7 of 30 patients and occurred exclusively in the double lung transplant group. Sepsis developed in three of the patients with this complication and they subsequently died. The risk of empyema was independent of preoperative diagnosis (p > 0.05). Of interest, all patients with cystic fibrosis (n = 3) with complicating empyema had Pseudomonas cepacia in the pleural fluid. Other miscellaneous complications included subpleural hematoma, chylothorax, and hemothorax. The latter two necessitated thoracic duct and bronchial artery ligation, respectively. In summary, a significant proportion of lung transplant recipients will have pleural space complications. The vast majority of these will resolve spontaneously or with conservative procedures. These complications were not related to preoperative diagnosis nor associated with a significant prolongation of hospital stay (p > 0.05). Empyema is the only pleural space complication associated with increased patient mortality and, as such, is an important clinical marker for those at risk for sepsis and death. (J THORAC CARDIOVASC SURG 1995;110:22-6)
Lung transplantation is an accepted treatment in selected patients with end-stage lung disease.
1-5 Although survival after lung transplantation was initially hindered by technical limitations, continued evolution of organ preservation methods, surgical techniques, and postoperative management has significantly improved the likelihood of allograft survival and function. 6-8
As our experience with lung transplantation increases, we have become aware of other complications that may lead to significant morbidity and mortality. One such area is that of pleural disorders. Pleural complications should not be surprising given that (1) the pleural space is completely exposed, (2) patients are immediately given immunosuppressive agents, (3) patients may have had previous pleural procedures and complications (such as open lung biopsies and pneumothoraces), (4) subgroups of patients have chronic sinopulmonary infection (that is, cystic fibrosis), and (5) frequent transbronchial biopsies are part of transplant surveillance protocols.
We therefore sought to examine the nature and frequency of pleural space complications in the Toronto Lung Transplant Program and their effect on patient outcome. Further knowledge of such complications may be useful in the future development of protocols to lessen their frequency and minimize morbidity.
PATIENTS AND METHODS
Between November 1983 and February 1993 a total of 53 single lung transplants (SLT) in 50 patients and 91 double lung transplants (DLT) in 90 patients were done. Eight patients have undergone retransplantation (3 SLT, 5 DLT). The indications for lung transplantation are listed in Tables I and II. Patient selection criteria have been described previously. 9
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Surgical technique
SLT.
Between November 1983 and May 1990, graft implantation was done in 39 patients according to a technique that included an omental wrap around the anastomosis. 6 Thereafter, the approach to bronchial anastomosis was changed to the telescoping technique described by Calhoon and associates. 8
DLT.
Initial transplantation was done en bloc in 13 patients with single venous and arterial anastomosis and a tracheal anastomosis; a second group of 5 patients underwent en bloc transplantation with single venous and arterial anastomosis, but bilateral bronchial anastomosis. Subsequently 22 patients underwent bilateral sequential SLT with separate vascular and bronchial end-to-end anastomoses. Since May 1990, all DLT procedures have been done with bilateral sequential single grafts with the telescoping bronchial technique.
Immunosuppression
From 1983 to 1989, induction immunosuppression consisted of Minnesota antilymphocyte globulin, cyclosporine, and azathioprine. Steroid administration was started 2 weeks after transplantation. Minnesota antilymphocyte globulin administration was started as a continuous infusion immediately after transplantation. The 10 to 20 mg/kg per day dosage was adjusted to achieve a desired lymphocyte count of 0.15 to 0.30 x 103/ml. This was discontinued when adequate cyclosporine levels were obtained, usually 5 to 7 days after transplantation.
Cyclosporine was given perioperatively 15 to 3.0 mg/kg per day by continuous infusion with conversion to the oral preparation at 5 to 10 mg/kg per day as soon as tolerated. The dose was adjusted to obtain a whole blood trough level of 250 to 300 ng/ml in the first year and 170 to 250 ng/ml thereafter. Azathioprine was given in a dosage of 1.0 to 2.0 mg/kg per day. Since 1990, perioperative steroids have been given as follows: methylprednisolone 500 mg intravenously before graft perfusion and for 4 days after transplant; then prednisone 0.5 mg/kg per day, tapering to 0.25 mg/kg during the first 6 to 9 months with a long-term maintenance dose after 1 year of 15 mg every other day.
Surveillance and diagnosis of rejection
Acute rejection is suspected when any of the following occur: dyspnea, fatigue, fever, increased alveolar-arterial gradient, arterial oxygen desaturation on exercise, chest x-ray film abnormalities, or a decline in forced expiratory volume in 1 second. Routine surveillance bronchoscopies have been instituted since 1988. Bronchoscopic examination with bronchoalveolar lavage and transbronchial biopsy is done every 3 months during the first year, every 6 months during the second year, yearly thereafter, and whenever rejection is suspected. 10
Study design
Charts from all cases of SLT and DLT were reviewed retrospectively and the type and frequency of pleural space complications were recorded. Pleural complications for the purposes of this review were defined as pneumothorax persisting beyond the first 14 postoperative days and responsible for extending hospital stay; recurrent pneumothorax; or any other pleural process that necessitated diagnostic or therapeutic intervention, or both. The pleural complication rate was compared among different diagnostic groups and between SLT and DLT recipients by the Student's t and 
2 tests (Table III). Length of hospital stay after transplantation was evaluated as a means of assessing patient morbidity. Length of stay for each diagnostic group was compared by analysis of variance. Data are expressed as mean plus or minus the standard error of the mean.
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Demographics
SLT was done in 27 women and 23 men. Three female patients underwent repeat SLT, which brought the total number of SLT procedures to 53. Mean ages were 42.5 ± 11.2 and 48.9 ± 11.1 years, respectively. Of the 91 DLT procedures, 35 were done in women and 55 in men. Four women with SLT underwent DLT and 1 woman had DLT twice. Three women underwent SLT twice. Mean ages were 39.5 ± 11.9 and 40.9 ± 13.4 years, respectively.
Types of complications
Of the 138 patients in the transplant population, 30 (22%) were observed to have postoperative complications of the pleural space. Pneumothorax was the most frequent pleural complication observed and accounted for 14 of 30 pleural space problems. There were seven cases of empyema and four of parapneumonic effusion also observed in the transplant population. Other pleural space disorders occurred less frequently (Table IV).
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Table V).
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Parapneumonic effusions occurred only in DLT and all resolved spontaneously. Empyema was observed only in DLT, with a frequency of 7 (8%) of 91. There was no difference in the frequency of empyema in patients with obstructive lung disease versus the frequency in those with septic lung disease (11% versus 8%, p > 0.05). One death related to sepsis occurred in each of the diagnostic groups with documented empyema: 
1-antitrypsin deficiency, emphysema, and cystic fibrosis. All patients with cystic fibrosis with complicating empyema (n = 3) had cultures positive for Pseudomonas cepacia. Patients with obstructive lung disease and complicating empyema had culture results showing methicillin-resistant staphylococcus (n = 1), mixed gram-negative cultures (n = 2), and Pseudomonas aeruginosa (n = 1). Clagett windows were required in two of seven patients with empyema. Empyema was the only pleural complication associated with death.
There was no significant difference in postoperative in-hospital length of stay between the SLT and DLT groups (Table VI). Similarly, no differences were observed when length of stay was compared among different preoperative diagnostic groups or between those patients with and without pleural complications.
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To date there has been only anecdotal discussion of pleural complications in the lung transplant literature. This has occurred within the context of several descriptive case series that outlined the spectrum of postoperative complications observed at individual transplant centers. 11, 12 Our experience shows that a significant proportion of the lung transplant population (30 of 138 or 22%) will have postoperative pleural space complications. The three most frequently observed complications were pneumothorax (14 of 30), empyema (7 of 30), and parapneumonic effusion (4 of 30). The nature of the procedure (SLT versus DLT) and the preoperative diagnosis did not influence the length of in-hospital stay or the type of pleural space complication. In our experience, the postoperative occurrence of either pneumothoraces or parapneumonic effusions was inconsequential. In the vast majority of cases these complications resolved spontaneously or with chest tube thoracostomy. They were never associated with increased patient mortality.
Empyema was the only pleural space complication associated with death. This was exclusively seen in the DLT population. This may reflect the increased infectious complication rate associated with the simultaneous violation of two pleural spaces in an immunocompromised host. Three of the seven patients in the empyema group died of sepsis-related complications. All patients with cystic fibrosis with empyema (3 of 7) had cultures positive for Pseudomonas cepacia; however, there was only one death in that group. Patients in the 1-antitrypsin deficiency group typically had mixed culture results. The only exception to this was one patient for whom the culture grew methicillin-resistant Staphylococcus aureus and who subsequently died with multiorgan system failure. The increased mortality associated with empyema did not appear to be associated with the presence of preoperative septic lung disease.
Raju and colleagues 11 noted a similarly bleak prognosis in a patient in their series in whom empyema developed. They described a 27-year-old woman with cystic fibrosis who underwent DLT. A postoperative empyema developed, which subsequently grew Pseudomonas aeruginosa. She died of septic complications on postoperative day 65.
A low prevalence of pleural complications was recently described in patients undergoing thoracotomy for lung carcinoma. 13 In this series of 103 consecutive patients, there were three patients in whom pleural complications developed. There was one case of empyema, which was not fatal. One case each of bronchopleural fistula and pneumothorax with prolonged air leak was described. These results provide an interesting contrast to our data. As previously discussed, we have hypothesized that simultaneous violation of two pleural spaces significantly increases the prevalence of observed pleural complications. In this lung carcinoma group undergoing thoracotomy, all patients had only unilateral violation of the pleural space. Furthermore, these patients were not receiving immunosuppresive therapy and one would intuitively anticipate a much lower prevalence of septic complications.
The vast majority of pleural complications in the postoperative lung transplant population appear inconsequential and are not associated with a significant prolongation of hospital stay. Empyema was the only pleural space complication associated with increased patient mortality. The occurrence of empyema in our study was independent of preoperative lung disease and therefore it is difficult to speculate about possible patient risk factors or modes of early intervention to offset its development. A heightened clinical suspicion for the presence of empyema must be observed and an aggressive approach to the diagnosis and treatment should be undertaken to prevent septic complications and death.
Footnotes
From the Departments of Medicinea and Surgery,b University of Toronto and The Toronto Hospital, Toronto General Division, Toronto, Ontario, Canada. 
References
This article has been cited by other articles:
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